Set in the 26th century, the story follows engineer Isaac Clarke, a crewman on a repair vessel assigned to the USG Ishimura, a massive planetary mining ship that has gone silent. While investigating a distress call sent by the ship's medical officer Nicole Brennan (Isaac's girlfriend), the vessel's crew is attacked by mutated human corpses; Isaac is forced to fend for himself as he tries to save his surviving crewmates and learn the truth behind the loss of Ishimura.
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