FP: LiceRESIST - Unravelling genetic mechanisms underlying sea lice resistance in salmonid fishes

Salmon lice (Lepeophtheirus salmonis) are the most significant animal welfare and economic challenge threatening the sustainability and expansion of salmon aquaculture. In many countries, these parasites have developed resistance to chemical treatments, and the lack of effective alternatives poses a serious risk to the industry's future growth. In the wild, brown trout and Atlantic salmon often suffer the heaviest lice infestations, characterized by high parasite burdens. By contrast, some Pacific salmon, particularly coho salmon, possess a machinery that enable them to eliminate salmon lice entirely. However, the underlying genetic mechanisms responsible for this resistance remain unclear. The main objective of LiceRESIST project was to uncover the genetic and epigenetic factors that drive species differences in susceptibility to lice infestation among salmonid fishes. Challenge tests were conducted in Canada, Chile, and Norway, using salmonid species with varying levels of susceptibility, including Atlantic salmon, rainbow trout, and coho. Tissue samples from skin and fins, both with and without lice, were analyzed to identify gene expression patterns and epigenetic changes associated with lice infestation. To deepen our insights into resistance mechanisms, the project developed and annotated high quality genome assemblies for the three species. These genome assemblies incorporated functional data (RNA-, ATAC-, and ChIP-data) generated during the challenge experiments. Bioinformatic and statistical analyses of the data highlighted specific immune response and wound-healing pathways as key drivers of resistance. Furthermore, the project established cell lines derived from various salmonid species, facilitating in-vitro gene editing to study lice resistance and wound-healing processes. These cell lines revealed distinct responses to lice exposure, with all demonstrating upregulation of stress-related, cell migration, and immune-related genes. Follow-up gene editing experiments provided insights into cell behavior, including migration, proliferation, and responses to artificial wounds and chitin, shedding light on mechanisms that contribute to the species differences in lice infestation. In summary, the LiceRESIST project has significantly advanced our understanding of the genetic and epigenetic basis of lice resistance. Its findings lay the groundwork for precision breeding programs aimed at developing a more lice resistant salmon. Moreover, the project introduced innovative in-vitro methods for studying host-parasite interactions, reducing the need for experiments on live fish. These developments mark important progress toward improving animal welfare and fostering a more sustainable aquaculture industry.

Sea lice infestations pose a significant threat to salmon production in many countries, including Norway, creating serious animal welfare concerns and causing widespread negative environmental impacts. The LiceRESIST project has made substantial progress in addressing this challenge, delivering advancements in genome functional annotation and providing novel insights into lice resistance mechanisms in salmonid species. These findings enhance the ability to predict sea lice resistance using genomic data and support the development of innovative strategies to combat sea lice infestations. Moreover, the data generated by LiceRESIST aligns closely with ongoing collaborative initiatives, including partnerships established through the project. These efforts aim to elucidate the functional basis of key commercial traits in aquaculture, ensuring that the project's outcomes will have value beyond its original scope.

Sea lice (Lepeophtheirus salmonis) is the single greatest biological threat to the development of sustainable salmonid farming. Despite extensive international research efforts, our understanding of the functional genetic basis for host immune responses to sea lice infestations in Atlantic salmon, the main farmed species in Norway, remains unclear, largely due to the complex genetic architecture of the trait. By comparing the functional genomic changes occurring in response to sea lice attack in several salmonid species exhibiting diversity in resistance, LiceRESIST will (i) reveal novel functional mechanisms underlying immunity that have evolved in independent lineages, and (ii) facilitate the identification of key causative genetic variants responsible for lineage-specific resistance to lice burden. Our approach, combining comparative and functional genomics with CRISPR/Cas gene editing for discovery and validation of functional differences, will create opportunities to devise novel therapeutics to combat the sea lice threat. Given the pressing nature of the sea lice problem for aquaculture, in terms of economic losses, animal welfare concerns, and the threat to wild salmon, generating such advanced knowledge as a basis for improved lice management is both urgently required and in full alignment with the vision of the HAVBRUK2 program.