Transcriptome changes in different immune cell types reveal divergent responses to rhabdovirus infection in resistant and susceptible rainbow trout

The genetic basis of host resistance to viral infections is generally shaped by complex interactions between host genetic variations affecting antiviral immunity and the rapid evolutionary adaptability of viruses. In this study, we investigated two isogenic rainbow trout lines exhibiting extreme resistance or susceptibility to the rhabdovirus VHSV. We compared transcriptomes of the pronephros a major lymphoid organ in fish at steady state and following VHSV infection. By integrating bulk tissue RNAseq with single cell RNseq, we mapped the divergent transcriptomic responses of resistant and susceptible fish to specific immune cell types. At steady state, differences in antiviral pathways were minimal. However, VHSV infection triggered markedly distinct transcriptomic shifts between the two lines. Both resistant and susceptible fish exhibited a broad transcriptional response enriched in core type I interferon (IFN) pathway genes. However, line-specific responses were enriched in genes induced by infection independently of type I IFN. In resistant fish, lymphocyte responses included type I IFN pathway genes, numerous transcription factors, and various cytokine receptors. In contrast, lymphocyte responses in susceptible fish involved only a limited set of type I IFN-induced genes. Monocytic cell responses also diverged: susceptible fish upregulated IFN-induced genes, while resistant fish showed increased expression of proinflammatory genes. This study provides a first detailed annotation of immune cell-specific transcriptomic responses to viral infection in fish from genetically resistant and susceptible backgrounds.