Co-infection with T. bryosalmonae infection triggered a broad transcriptional response in rainbow trout, marked by upregulation of 1562 genes including cytochrome P450 family 24 subfamily A member 1 (CYP24A1), F-box protein 32 (FBXO32), complement C4B chido blood group (C4B), chromosome X open reading frame 65 (CXorf65), interferon induced protein 44 (IFI44), and pyruvate dehydrogenase kinase 2 (PDK2), associated with immune signaling, metabolic regulation, and cellular stress adaptation. Here, C4B is linked to coinfection.