Limited polar geographical range, narrowly defined migratory routes, and deep-diving behaviours make narwhals exceptionally vulnerable to anthropogenic disturbances including oceanic noise. Although behavioural studies indicate marked responses of cetaceans to disturbance, the link between fear reactions and possible injury from noise exposure is limited for most species. To address this, we deployed custom-made heart rate-accelerometer-depth recorders on 13 adult narwhals in Scoresby Sound, East Greenland across a five-year period (2014–2018). Physiological responses of the cetaceans were monitored in the absence (n = 13 animals) or presence (n = 2 animals across 3 acoustic events) of experimentally directed, seismic airgun pulses and associated vessels (full volume source level = 241 dB re 1 μPa-m). We found that anthropogenic noise resulted in marked cardiovascular, respiratory and locomotor reactions by two narwhals exposed to seismic pulses across three acoustic events. The general behavioural response to seismic and vessel noise included an 80% reduction in the duration of gliding during dive descents by seismic-exposed narwhals compared to controls, and the prolongation of high intensity activity (ODBA > 0.20 g) with elevated stroke frequencies exceeding 40 strokes per minute. Noise exposure also resulted in intense (<10 bpm) bradycardia that was decoupled from stroking frequency. This decoupling instigated increased variability in heart rate, with the heart switching rapidly between bradycardia and exercise tachycardia during noise exposure. The maximum respiratory frequency following seismic exposure, 12 breaths/min, was 1.5 times control levels. Overall, the effect of seismic/ship noise exposure on Arctic narwhals was a 2.0–2.2-fold increase in the energetic cost of diving, which paradoxically occurred during suppression of the cardiac exercise response. This unusual relationship between diving heart rate and exercise intensity represents a new metric for characterizing the level of fear reactions of wild marine mammals exposed to different environmental stressors. Together, the multi-level reactions to anthropogenic noise by this deep-diving cetacean demonstrated how a cascade of effects along the entire oxygen pathway could challenge physiological homeostasis especially if disturbance is prolonged. Read the free Plain Language Summary for this article on the Journal blog.