Fish venoms constitute highly specialized biochemical systems, yet their molecular composition and gene-expression architecture remain poorly resolved in many venomous teleosts. In lionfishes, venom is delivered through fin-associated spines, but transcriptome-level insights into spine-specific venom production are largely absent, particularly for the dwarf lionfish Neochirus brachypterus. The lack of species-specific molecular resources has hindered systematic identification of venom-associated genes, functional pathways, and evolutionary relationships of toxins within this lineage. Addressing this knowledge gap, the present study provides the first comprehensive transcriptomic analysis of venomous spine tissue in N. brachypterus (Dwarf lionfish), a poorly characterized lionfish species. Functional annotation against the NR and UniProt Swiss-Prot databases revealed a substantial portion of unannotated transcripts reflecting current limitations in assembly completeness. However, InterProScan analysis identified 1459 unique Pfam domains and 599 superfamilies, indicating a functionally diverse transcriptome enriched in structural, signaling, and transport-related domains. Gene Ontology (GO) enrichment analysis further highlighted the metabolic and regulatory complexity of the venom-producing tissue. Notably, similarity searches against venom and toxin databases identified seven putative toxin homologs, including neoverrucotoxin, stonustoxin, verrucotoxin, and 5′-nucleotidase. These sequences exhibited significant homology to venom components reported from other Scorpaeniformes and distantly related venomous taxa, including snakes, reflecting convergent molecular features rather than shared ecological or functional equivalence. The presence of these toxin-like transcripts suggests potential roles in tissue damage, nociception, and physiological disruption during envenomation, consistent with a defensive venom system. Collectively, this transcriptomic resource advances understanding of the molecular repertoire underlying Neochirus brachypterus venom and establishes a foundation for future studies on the evolution, diversification, and pharmacological potential of lionfish toxins.
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