Immune divergence in rainbow trout lines selectively bred for F. psychrophilum resistance or susceptibility revealed by challenge with Weissella tructae.

Host genetic resistance can be improved through selective breeding, yet underlying immune mechanisms often remain unknown due to varying pathogen burden. In previous research, rainbow trout lines, ARS-Fp-R (resistant, R-line) and ARS-Fp-S (susceptible, S-line), were bred for differential resistance to Flavobacterium psychrophilum, but mechanisms remain unclear and study has been confounded by the higher F. psychrophilum load in the susceptible line. Here, we separate line-specific traits from pathogen-load driven effects, by challenging with Weissella tructae, a pathogen for which both lines exhibit equivalent susceptibility. After 3 to 6 days post-challenge with W. tructae, we report the divergent and shared cellular and cytokine profiles. The infected R-line fish exhibited higher granulocyte levels post-challenge, a trait also observed in its response to F. psychrophilum, while S-line fish had a more severe depletion of circulating leukocytes and IgM + B cells. Proteomic analysis identified 50 infection-induced blood proteins. Using novel salmonid biomarker assays, the S-line exhibited a 6-fold higher tumor necrosis factor-alpha (TNFα) and elevated precerebellin (PCB). In contrast, the R-line showed 3-fold higher baseline complement factor H-like-1 protein (CFHL-1), and a trend toward elevated serum amyloid A (SAA). Other biomarkers, including Cath2, GDF-15, haptoglobin, and C1q-LP3 increased post-infection but did not differ between lines. Both lines exhibited similar granulomatous epicarditis and decreased plasma fibrinogen. Despite equivalent susceptibility to W. tructae, these lines demonstrate divergent cellular and cytokine responses, suggesting a shift in immune architecture due to selective breeding. The novel biomarker assays provide valuable tools for monitoring immune health and precision breeding in salmonid aquaculture.