Dissecting the host transcriptome and microbiota responses to Viral Hemorrhagic Septicemia Virus (VHSV) in the turbot (Scophthalmus maximus) intestine: insights from moribund and asymptomatic phenotypes

Viral infections profoundly influence host physiology, not only by triggering complex immune responses but also by reshaping the associated microbiota. Conversely, the microbiota can modulate antiviral defenses and disease outcomes through its interactions with the host immune system. This dynamic triad -virus, microbiota, and host immunity- has emerged as a central determinant of infection severity and recovery. Yet, despite growing evidence from mammalian models, its functional implications in fish remain poorly understood. Here, we investigated the effects of viral hemorrhagic septicemia virus (VHSV) infection on the intestinal transcriptomic and microbiota profiles of turbot ( Scophthalmus maximus ), an aquaculture species highly susceptible to this pathogen. Comparative analyses were conducted among asymptomatic and moribund fish at 10 days post-infection, and uninfected controls. Transcriptomic data revealed that moribund individuals exhibited a dysregulated immune response characterized by a strong induction of complement- and coagulation-related genes and other inflammatory pathways, whereas asymptomatic fish displayed expression patterns more closely resembling those of uninfected controls, indicating a more controlled or resolved immune activation. Microbiota analyses showed that VHSV infection induced widespread, severity-dependent changes in the intestinal microbiota, with progressive shifts in the relative abundance of most bacterial taxa from controls to asymptomatic and moribund fish. Interestingly, a subset of bacterial genera deviated from this general trend, displaying an opposite pattern to that observed in both uninfected and moribund individuals, suggesting their potential involvement in resistance mechanisms. Integrative analyses further revealed significant correlations between specific bacterial genera and host genes differentially expressed between asymptomatic and moribund fish, highlighting functional links between microbial composition and immune regulation. Together, these findings reveal complex interactions between VHSV infection, host immunity, and microbiota composition in turbot, providing novel insights into host-microbe-virus relationships that may inform disease management and selective breeding strategies in aquaculture. • VHSV triggered strong complement and coagulation gene expression in moribund fish • VHSV caused intestinal dysbiosis with increases in opportunistic bacteria • Asymptomatic fish showed microbial signatures potentially linked to resistance