Thermal modulation of genetic resistance to infectious salmon anemia virus: Transcriptome analyses of Atlantic salmon families (Salmo salar) at 10 °C and 20 °C

Understanding the interaction between genetic resistance and environmental temperature is critical for managing infectious salmon anemia virus (ISAv) in Atlantic salmon aquaculture. Building upon an experimental infection trial of 20 families with ISAv HPR4 at 10°C and 20°C, we conducted RNA sequencing of head kidney samples from the two most resistant (average survival: 81% at 10°C, 93% at 20°C) and two most susceptible families (average survival: 32% at 10°C, 54% at 20°C). Transcriptomic analysis revealed that resistance mechanisms were dramatically temperature-dependent, with 3,690 differentially expressed genes (DEGs) between resistant and susceptible families at 10°C compared to only 64 DEGs at 20°C. At 10°C, resistance was characterized by coordinated downregulation of proteasome, DNA replication, and translation initiation pathways, alongside upregulation of receptor internalization mechanisms including flotillin proteins, β-arrestins, and NEDD4 E3 ubiquitin ligase. Temperature comparisons revealed fundamentally different molecular strategies: resistant families (7,156 DEGs) prioritized DNA replication, cell cycle processes, and oxidative phosphorylation, while susceptible families (8,004 DEGs) emphasized RNA processing, ribosome biogenesis, and proteasome-mediated protein degradation. Genome-wide association analysis identified the translation initiation factor EIF4G1 on chromosome 14, which was significantly downregulated in resistant fish (log₂FC = -0.51, FDR = 0.03). These findings demonstrate that ISAv resistance relies on broad cellular resilience strategies rather than classical antiviral responses, and that these mechanisms interact substantially with thermal conditions.