Subnautica takes place in the late 22nd century, when humanity begins to colonize other star systems. The Aurora, a deep-space vessel constructed by the Alterra Corporation, has been sent to a system at the outer reaches of known space on its maiden voyage. Its primary mission is to build a section of high-speed space travel infrastructure known as a Phasegate in the Ariadne wing of the galaxy. However, its secondary mission, unknown to most of the crew, is to search for and, possibly, rescue the crew of a ship called the Degasi, which crashed on planet 4546B ten years prior. After the Aurora enters orbit of 4546B, it is physically waylaid by a mysterious force and crash-lands on the planet. Several crew members climb into lifepods and jettison from the Aurora during the descent, one of whom is the player character. The other lifepods' inhabitants perish through various means, leaving the player as the lone survivor. The player finds records of the Degasi's crew stating that only three survived the initial crash, but later two out of the three are confirmed dead and one is presumed dead.
The player also learns of the existence of the Precursors, an ancient, advanced alien species that came to planet 4546B approximately one thousand years ago in search of a cure for a highly infectious disease, known as the Kharaa Bacterium. The Precursors discovered the Kharaa during the exploration of an unknown planet, and the disease spread due to a failure in quarantine procedures, killing over 100 billion individuals. The disease was released into the ecosystem of 4546B in a catastrophic accident, where a Sea Dragon Leviathan attacked the Disease Research Facility where the bacteria sample was being researched in an attempt to retrieve its stolen egg, causing the Precursors to initiate planetary quarantine. They did this by activating the automated Quarantine Enforcement Platform, a massive alien weapon system, that shoots down ships that attempt to land or leave, in order to stop the bacterium from spreading to other worlds. The Aurora crashed because it appeared to be landing on the planet. The player witnesses another ship, the Sunbeam, get shot down after it had detected the Aurora's distress signal and attempted to rescue any survivors. When the player attempts to deactivate the weapon, it fails due to the player being "infected". In order to leave the planet, the player must locate the Precursors' Primary Containment Facility deep underground to find a gigantic creature known as the Sea Emperor Leviathan.
The Sea Emperor is the last of its kind, and will telepathically communicate with the player throughout the game, encouraging them to locate her and letting her help the player. It has been keeping the life in the area alive by using small fish-like creatures known as "Peepers" to distribute small amounts of a degraded form of the cure, Enzyme 42, which is produced by the Sea Emperor itself. This keeps the planet's flora and fauna alive but it is insufficient to eradicate the plague, due to the Sea Emperor's age of over one thousand years, and thus deteriorating health. The Precursors recognised Enzyme 42 as a possible cure, but since the enzyme produced by the Sea Emperor was insufficient, they turned their focus on its eggs, as they believed the Sea Emperor's young would produce the cure in a purer form. They attempted to artificially hatch the eggs, but were unsuccessful, and eventually abandonded the program. Once found, the Sea Emperor will give the player the recipe for the Hatching Enzymes, which are made from various flora, and upon using will trigger a hatching response in the eggs. The player crafts the Hatching Enzymes, and the Sea Emperor's young hatch. They produce the Enzyme 42 and the player is cured of the infection. The young then leave the base, spreading the enzyme and curing the rest of the planet. The player is then free to disable the Quarantine Enforcement Platform.
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