Integrated transcriptomic and histopathological analyses reveal the potential mechanism of Litopenaeus vannamei against the translucent post-larvae disease

Pacific white shrimp (Litopenaeus vannamei) is the most important farmed crustacean species worldwide, contributing over 80% of global shrimp production. However, its farming industry has recently been severely challenged by translucent post-larvae disease (TPD), a newly emerging syndrome caused by Vibrio parahaemolyticus (VpTPD), which induces over 90% mortality in post-larval shrimp within a few days. Yet how VpTPD drives the cascade from early infection to rapid mortality-via coordinated changes in histopathology and gene expression-remains unclear. Understanding the host responses to this pathogen is therefore essential for disease control and breeding of resistant stocks. In this study, we integrated histopathological examination with hepatopancreatic transcriptomic analysis to characterize the pathological changes and immune-metabolic responses of shrimp infected with VpTPD. Histological results revealed severe multi-organ lesions, with the hepatopancreas and midgut being the most susceptible tissues, showing tubular epithelial necrosis, massive sloughing, vacuolization, and infiltration of hemocytes. Transcriptomic profiling further demonstrated extensive modulation of immunity-, metabolism-, and stress-related pathways. Key effector genes, such as phenoloxidase subunit 1-like, prophenoloxidase-activating factors, and antimicrobial peptides including crustins, were significantly upregulated, reflecting activation of defense cascades. Conversely, several pathogen recognition molecules, including multiple C-type lectins and hemocyanin subunits, were markedly downregulated, indicating impaired recognition and reduced availability of immune substrates. These results demonstrate that TPD in shrimp is characterized by profound immune imbalance, in which canonical recognition molecules are suppressed while compensatory receptors and immune effectors are induced. This imbalance indicates that although the shrimp immune system is strongly stimulated, the lack of proper recognition and functional substrates may reduce the efficiency of pathogen clearance, leading to persistent infection and tissue damage. Overall, our results highlight that host immune regulation plays a decisive role in the pathogenesis and control of TPD, and offer new insights for understanding disease mechanisms and guiding future prevention strategies in shrimp aquaculture.