Tissue-Specific Transcriptomic Insights into Myxozoan Infections: Immune and Stress Responses in the Kidney and Head...

By damaging target tissues and compromising the host immune system, Myxobolus cerebralis and Tetracapsuloides bryosalmonae remain persistent threats to salmonids. RNA sequencing was used to assess transcriptome modulation in the kidney and head cartilage (HC) of rainbow trout during single and co-infections with these two myxozoan parasites. Fish were exposed to M. cerebralis (Mc) and T. bryosalmonae (Tb), and 30 days later, half of the fish from each group were subjected to sequential co-infections (Mc⁺ and Tb⁺). This assessment aimed to evaluate the combined effects of both pathogens. Transcriptomic analysis was conducted using kidney and HC tissues collected 60 days post-co-infection. The results showed that infection order altered host transcriptional profiles in a tissue-dependent manner. In the kidney, Tb fish showed pronounced transcriptional alterations linked to chronic inflammation, immune complex clearance, and IL-8-mediated responses. Tb⁺ fish exhibited broad immune activation in the kidney, suggesting dysregulated inflammatory responses likely associated with subsequent infection with M. cerebralis. In the kidney of Mc⁺ fish, the immune response was characterized by macrophage and IL signaling pathways. In HC, Mc fish activated Th17, IL-23, phagolysosome, and IL-6 cytokine pathways. In contrast, Mc⁺ fish showed increased pathogen processing and enhanced metabolic responses accompanied by suppression of cytokines and tissue repair processes. HC responses in Tb⁺ fish shifted toward IL-23, Th17-driven responses, alongside reduced developmental and extracellular matrix processes. The study establishes that host responses to myxozoan co-infection are shaped by tissue tropism and infection sequence, with distinct immune and tissue remodeling pathways activated in the target organs. These findings enhance the understanding of sequential T. bryosalmonae and M. cerebralis infections and provide a basis for identifying tissue-specific biomarkers and key immune targets. The findings may help identify methods for improved monitoring and management of myxozoan infections in salmonids.