Hematology-centered characterization of systemic host responses and atypical circulating cells during Aeromonas salmonicida subsp. salmonicida infection in mandarin fish (Siniperca scherzeri).

Aeromonas salmonicida subsp. salmonicida is an important bacterial pathogen causing systemic disease in cultured fish, but the associated hematological responses remain poorly understood. This study characterized temporal host responses following experimental infection in mandarin fish (Siniperca scherzeri) using a hematology-centered approach integrating complete blood count, blood biochemistry, leukocyte morphology, and comparative immune gene expression in peripheral blood and kidney. Experimental infection caused approximately 60% cumulative mortality. Conventional leukocyte parameters remained largely unchanged, whereas platelet counts increased approximately sixfold at 2 days post-infection (dpi). Circulating triglyceride levels progressively declined by approximately 68% and represented the highest-ranked variable in multivariate analyses. Peripheral blood smears revealed marked leukocyte remodeling characterized by vacuolization, nuclear abnormalities, and cytoplasmic disruption. Most notably, atypical circulating leukocyte-like cells transiently emerged at 4-6 dpi and were classified into three distinct morphological phenotypes. Immune gene expression analyses revealed compartment-specific responses, with most immune-related genes peaking at 3 dpi in peripheral blood, whereas delayed but sustained activation occurred in the kidney, where IL6 expression increased up to 67-fold at 8 dpi. These findings demonstrate coordinated yet compartment-specific hematological, metabolic, molecular, and cytological responses despite relatively limited alterations in conventional hematological parameters. This study establishes a hematology-centered disease trajectory for A. salmonicida subsp. salmonicida infection and highlights the value of integrated blood-based profiling for characterizing distinct host responses during bacterial disease progression.