Integrated molecular and genetic insights into Bald sea urchin disease in Tripneustes gratilla (Linnaeus, 1758)

Bald sea urchin disease (BSUD) has emerged as a significant threat to the aquaculture of Tripneustes gratilla , causing substantial mortality. Despite its economic importance, the host’s molecular response to BSUD remains poorly characterized. This study presents the first integrative analysis combining transcriptomics, histopathology, and population genetics to elucidate the dynamics of disease response across asymptomatic, symptomatic, and recovery stages in T. gratilla . Transcriptomic profiling revealed distinct gene expression patterns across disease stages, with early activation of innate immune-related pathways, alongside cytoskeletal remodeling processes in the asymptomatic group. These molecular signals were accompanied by histological evidence of early epithelial thinning and tube foot detachment. In symptomatic sea urchins, gene expression shifted toward stress responses and metabolic reprogramming, notably involving NADPH production and the pentose phosphate pathway. Recovery-stage sea urchins showed enriched pathways related to actin organization, muscle contraction, and glycolysis, consistent with tissue regeneration and functional restoration. qPCR validation confirmed elevated expression of lysozyme, actin, and plexin-A4-like transcripts in asymptomatic sea urchins, supporting their potential as early molecular markers for BSUD detection. Genetic analysis also revealed the association of specific haplotypes with disease susceptibility, suggesting a role of restricted genetic background in host vulnerability. Together, these findings highlight early immune priming, cytoskeletal disruption, and metabolic plasticity as central features of T. gratilla ’s response to BSUD. The study offers valuable molecular markers and mechanistic insights for developing early diagnostic tools and disease mitigation strategies in sea urchin aquaculture. • The early BSUD stage is characterized by immune activation and cytoskeletal remodeling. • Symptomatic urchins exhibit metabolic shifts and oxidative stress response. • The recovery stage involves tissue regeneration and the restoration of muscle function. • Actin and lysozyme are potential biomarkers for BSUD early detection. • Genetic haplotypes may influence BSUD susceptibility in T. gratilla .