Histo-anatomical atlas of Garra rufa and its thermal tolerance at human body temperature

Abstract Garra rufa , the doctor fish, is a small freshwater cyprinid notable for its exceptional tolerance to high temperatures, surviving at the human body temperature of 37 °C, and has emerging potential as a novel laboratory model for human cancer xenotransplantation and infectious disease research. To establish a foundation for its experimental use, we conducted comprehensive histo-anatomical analyses across major organ systems. The overall body organization and tissue architecture of G. rufa are broadly similar to those of zebrafish ( Danio rerio ), indicating a conserved cyprinid body plan. However, several organ systems in G. rufa exhibit species-specific differences from zebrafish, including a well-developed adhesive disc around the oral region, a long and coiled intestine, and distinct dark pigmentation of the peritoneum. These species-specific traits may reflect ecological and behavioral adaptations of G. rufa , including benthic scraping in warm, flowing habitats. Physiological assays showed that G. rufa maintained high survival rates and total swimming distance at 37 °C, whereas zebrafish exhibited significant mortality and a reduction in total swimming distance under the same conditions. Collectively, this study provides a comprehensive histo-anatomical atlas of G. rufa and documents its marked tolerance to 37 °C. Although the underlying molecular mechanisms remain unresolved, these findings establish a foundation for future mechanistic studies of high-temperature tolerance and for evaluation of its suitability as an experimental fish species.