Simple SummaryThe deposition of excessive collagen resulting in scarring is a detrimental outcome of the wound healing process in humans, ultimately impeding the successful restoration of skin function. Surprisingly, in Fraser’s dolphins (Lagenodelphis hosei), collagens undergo a configuration change during wound healing and eventually recover to normal architecture. However, little research has been conducted on dolphins’ collagen composition in the skin and the underlying mechanism during the wound healing process. Here, histochemical staining and immunostaining were performed on normal and wounded skin samples in different healing stages of Fraser’s dolphins. The results demonstrate that collagens changed in composition during the wound-healing process. The mature healed wound implies the great ability to remove excessive collagen depositions in hypertrophic-like scars in Fraser’s dolphins. A better understanding of collagen dynamics in Fraser’s dolphins would provide more information and possibilities for solving aberrant scarring problems in humans.AbstractFraser’s dolphins (Lagenodelphis hosei) possess great healing abilities. Their skin composition can be restored after wounding, including collagen spacing, orientation, and bundle thickness. However, it remains unclear how collagens are involved in the wound-healing process and eventually regain normality in Fraser’s dolphins. Learned from the other two scarless healing animals, changes in type III/I collagen composition are believed to modulate the wound healing process and influence the scarring or scarless fate determination in human fetal skin and spiny mouse skin. In the current study, Herovici’s, trichrome, and immunofluorescence staining were used on normal and wounded skin samples in Fraser’s dolphins. The results suggested that type I collagens were the main type of collagens in the normal skin of Fraser’s dolphins, while type III collagens were barely seen. During the wound healing process, type III collagens showed at early wound healing stages, and type I collagen increased in the mature healed wound. In an early healed wound, collagens were organized in a parallel manner, showing a transient hypertrophic-like scar, and eventually restored to normal collagen configuration and adipocyte distribution in the mature healed wound. The remarkable ability to remove excessive collagens merits further investigation to provide new insights into clinical wound management.