Histopathological and biochemical evidence of neuroinflammatory involvement in Yersinia ruckeri-infected rainbow trout (Oncorhynchus mykiss): A multi-center field study.

While Yersinia ruckeri is known for causing systemic vascular damage, its potential to invade the central nervous system remains poorly understood. This study investigated the spatiotemporal distribution, pathological progression, antimicrobial resistance (AMR), and biochemical alterations associated with Y. ruckeri across 12 commercial rainbow trout farms in Türkiye. Advanced diagnostics using MALDI-TOF MS enabled rapid and accurate identification of the pathogen. Disease prevalence peaked in farms experiencing thermal stress (18 °C) and high biomass density. Histopathological examination revealed inflammatory alterations suggestive of neural involvement, including perivascular cuffing, neuronal degeneration, and focal neuroinflammation. In addition, Y. ruckeri was isolated from brain tissue in 15 infected fish and confirmed by MALDI-TOF MS, supporting the possibility of central nervous system involvement during systemic infection. Furthermore, the observation of neuroinflammation and perivascular cuffing suggests that the pathogenesis of Y. ruckeri is not limited to systemic vascular damage but also involves the central nervous system, which may explain the distinct behavioral changes and complex clinical progression of the disease. Antimicrobial susceptibility testing showed consistent multidrug resistance to amoxicillin, gentamicin, netilmicin, erythromycin, and sulfisoxazole. Serum biochemical analysis confirmed significantly elevated ALT levels, with ROC analysis identifying ALT as an excellent early biomarker (AUC = 0.956), having an optimal cut-off value of 71.4 U/L with high sensitivity (91.8%) and specificity (92.5%). The identified ALT threshold may provide a practical biomarker for the early detection and monitoring of ERM under field conditions. Collectively, this study provides new insights into ERM pathogenesis and highlights the need for improved antimicrobial stewardship and environmental risk management in aquaculture.