As many as 100 million salmonid fish are tagged annually by removing the adipose fin, usually for recovery statistics and the fishing industry. In a multi-parametrical approach, we evaluated the response to resection of the adipose fin in rainbow trout Oncorhynchus mykiss over the course of 72 h. Both the concentrations of lactate and the cerebral transcriptomes differed in rainbow trout early after adipose fin clipping compared to the matching intact controls. The number of differentially expressed genes significantly increased, first in the midbrain and later in the forebrain, in fin-clipped compared to intact trout. Several of these genes were predicted to be involved in pain-induced and synaptogenesis-related pathways, suggesting that adipose fin resection may affect the architecture of neuronal networks. In an experimental setup applying swimming tunnels, we tested whether removal of the adipose fin had any consequences on the behavior of fin-clipped versus intact trout exposed to a regularly recurring water flow. Concomitant with increased and prevailing breath frequencies after repeated exposure to water flows, we observed a marked transcriptional response in the forebrain of fin-clipped trout compared with intact unchallenged controls at later time points after the resection. The resulting list of differentially expressed genes was assigned to a broad range of signaling pathways involved in trans-synaptic signaling, neuronal interaction dynamics, and neuroplasticity. Taken together, our findings suggest that resection of the potentially flow-sensory adipose fin alters pathways related to pain perception and likely enhances the physiological response to the current, probably indicating increased physical effort. We also deduce from the transcriptomic data that amputation of the adipose fin leads to reorganization of the high-level integration system in the brain. The short-term effects observed in the present study require further validation to estimate the prevailing stress for the organism. Nevertheless, we propose considering alternative tagging methods for salmonid fish that do not conflict with fish welfare, as the amputation of the adipose fin may have more far-reaching physiological effects than previously assumed.